肿瘤微环境与肿瘤相互作用形成了有利于肿瘤生长、转移、复发的条件，构成抵抗肿瘤治疗的壁垒。我们在研究中发现，地塞米松与抗癌药物联用的纳米递药系统，程序性释放，修复肿瘤微环境，显著地抑制了肿瘤生长和转移。基于肿瘤微环境的特点和多靶点治疗的机理，我们以地塞米松和唑来膦酸为主要的模型药物，构建特异靶向M2型巨噬细胞和肿瘤细胞的多功能纳米递药系统。首先修复肿瘤微环境，调节肿瘤微环境中的炎性因子和细胞，激活免疫系统，逆转免疫抑制与阻断免疫逃逸，抑制血管新生，增加肿瘤血管灌注，降低肿瘤的间质液压，拆掉“壁垒”。随后针对肿瘤细胞和肿瘤微环境进行多靶点治疗，协同提高肿瘤的治疗效果，降低毒副作用。在分子、细胞、组织和整体动物水平上开展肿瘤和微环境交互作用的研究，在纳米药物提高肿瘤治疗效果领域取得一批原创性的重要研究成果，提高我国在纳米生物医药领域的国际竞争力。

Crosstalk between neoplastic and stromal cells contributes to tumor growth, progression and recurrence. Tumor microenvironment provides appropriate conditions for tumor growth and metastasis, and builds a “fence” to resist tumor treatment. In our previous study, we found that dexamethasone combined with antitumor drugs in nanoscale delivery system which possessed procedural releasing specialty, acted on tumor microenvironment and neoplasm, remodeled or re-educated the tumor microenvironment, significantly inhibited tumor growth and metastasis. Based on the characteristics of the tumor microenvironment and the mechanism of multiple targets treatment for tumor, with dexamethasone and zoledronate as the main drugs, we build a novel nano-drug delivery system for specific targeting to M2 macrophages and tumor cells. The nano-drug delivery system has diversified abilities on remodeling the tumor microenvironment, such as modifying of inflammatory cytokines and monocyte, activating the immune system, reversing immunosuppression and blocking immune escape, decreasing angiogenesis, promoting vascular perfusion, and reducing tumor high interstitial fluid pressure. So the “fence” is pulled down and tumor is exposed to drugs, paving the way for tumor therapies in multimodality and synergy therapeutic mechanisms. Meanwhile, the nano-drug delivery system could reduce the drug distribution in normal tissue, and minimize drugs dosage, therefore to reduce the side effects of drugs. According the crosstalk between tumor and its microenvironment on the molecules, cells, tissues, and whole animal levels, we engage to obtain a number of originality researches in the nano-drug to improve the effect of tumor treatment, and to improve the international competitiveness in the nano-medicine filed.